33 research outputs found

    Simple coupling reaction between amino acids and weakly nucleophilic heteroaromatic amines

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    International audienc

    Naphthyl and Coumarinyl Biarylpiperazine Derivatives as Highly Potent Human beta-Secretase Inhibitors. Design, Synthesis, and Enzymatic BACE-1 and Cell Assays.

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    International audienceTwenty novel ñ-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinylseries were designed for their potential use in Alzheimer’s disease therapy. Enzymatic and cell-based assayshave been carried out. The biological results clearly demonstrate that specific substituents located at theN4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between40 and 70 nM). Variable temperature NMR and modeling studies are consistent with the obtained biologicaldata, since these studies confirmed that introduction at the N4-position of the piperazine ring allows productiveinteractions within the BACE-1 active site, which appear to be determinative for high BACE-1 inhibitoryactivity. These results are of particular interest since some of the new analogues belonging to the naphthylseries are almost one log more active than the best inhibitor of the similar family recently reported
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